Cardiac output (CO) is the amount of blood the heart pumps out over a unit of time. Typical values of CO in resting adults range from 3 liters/minute to 6 liters/minute. One basis for estimating or measuring CO is the formula CO=HR×SV, where SV is cardiac stroke volume and HR is heart rate. If SV is measured in liters/beat and HR is measured in beats per minute, then CO is given in liters/minute, although any other units of volume and time may be used. Another basis for estimating or measuring CO is the formula CO=MAP/TPR, where MAP is mean arterial blood pressure and TPR is total peripheral resistance.
Cardiac output (CO) is a key hemodynamic variable that is commonly used to establish differential diagnoses, monitor disease progression, and titrate therapy in many cardiovascular conditions. For example, when combined with estimates of other hemodynamic variables such as mean arterial blood pressure (MAP) and total peripheral resistance (TPR), estimates of cardiac output may allow clinicians to determine the cause of circulatory shock. [1]. (Numbers in square brackets refer to the reference list included herein. The contents of all these references are incorporated herein by reference.)
The current clinical gold-standard for measuring CO is intermittent thermodilution, a highly invasive procedure in which a balloon-tipped catheter (Swan-Ganz catheter [2]) is advanced to the pulmonary artery, a bolus of cold saline is injected into the circulation, and the blood's temperature profile is observed as a function of time. Due to its high degree of invasiveness, this procedure is usually reserved for only the sickest of patients, and even in critical care its benefit is increasingly questioned as retrospective clinical studies in the past ten years conclude that the use of a pulmonary artery catheter may not improve patient outcome [3], [4]. There are several patents that disclose systems directed to estimating CO via thermodilution. Some examples include U.S. Pat. No. 4,236,527 to Newbower et al., U.S. Pat. No. 4,507,974 to Yelderman, U.S. Pat. No. 5,146,414 to McKown et al., and U.S. Pat. No. 5,687,733 to McKown et al. The disadvantage of these systems is that they are highly invasive, and that CO can only be measured intermittently. In many situations, e.g. in critical care units, CO measurements via thermodilution may be made only every 2-3 days.
It is possible, however, to obtain estimates of cardiac output without using highly invasive procedures: rather than intermittently measuring average cardiac output invasively via thermodilution, many attempts have been made to estimate CO from the arterial blood pressure (ABP) waveform [5], [6], [7], [8], [9], [10], [11], using models of the arterial system. One of the most basic of these models is the Windkessel model [5] (see FIG. 3a), in which the arterial tree is modeled as a single, leaky pressurized chamber that is filled intermittently with boluses of fluid. Because HR is usually easy to measure using any of a wide variety of instruments, the calculation of CO usually depends on some technique for estimating stroke volume. Conversely, any method that yields a value for CO can be used to determine SV. In addition, estimates of CO (or SV) can be used with HR to estimate any parameter that can be derived from either of these values.
An entire class of patented or patent-pending algorithms is based on analyzing the pressure pulse morphology, often in the context of Windkessel-like models for the arterial tree [6], [7], [8], [9], [12]. Examples of these are U.S. Pat. No. 5,400,793 to Wesseling, U.S. Patent Application Publication No. 20050124903 to Roteliuk et al., U.S. Patent Application Publication No. 20050124904 to Roteliuk, U.S. Patent Application Publication No. 20060235323 to Hatib et al., U.S. Patent Application Publication No. 20080015451 to Hatib et al., the contents of each of which are incorporated herein in their entirety. In many of these, since stroke volume is related to the arterial pressure pulse through the properties of the arterial tree, SV (and hence CO) is estimated on an intra-cycle timescale using morphological features of each individual ABP wavelet (such as systolic, mean, or diastolic ABP). One significant disadvantage of most of these methods or systems for estimating cardiac output is that they do not provide beat-to-beat estimates of cardiac output.
More recently, Cohen et al. ([10], [13], and U.S. Patent Application Publication No. 20040158163 to Cohen et al., the contents of which are incorporated herein in their entirety) intermittently, i.e. every 3 minutes, estimated relative changes in cardiac output from the inter-cycle (or beat-to-beat) variations of the ABP waveform, using these to determine the impulse response function of a model of significantly higher order than the Windkessel model and, from it, the time constant of arterial outflow that would be associated with a Windkessel model. Knowing the latter, the authors determined proportional CO, from which absolute CO can be obtained via calibration with a single or multiple reference CO measurements. In their calibration, Cohen et al. assume a linear relationship of arterial volume to mean pressure relationship, corresponding to constant lumped arterial tree compliance in the Windkessel model. Applicants' own interest in estimating CO and TPR derives from their own work in the area of cycle-averaged models of the cardiovascular system [14], [15], [16], where again the focus was on inter-cycle variation.
A criticism of Cohen et al. put forward in U.S. Patent Application Publication No. 20060235323 to Hatib et al. is that the approach disclosed by Cohen requires determination of a calibration factor on which accuracy of the CO measurement is closely dependent. Hatib et al. argue that Cohen's method ignores much of the information contained in the pressure waveform. In fact, as Hatib et al. note, one embodiment of Cohen's method uses only a single characteristic of each waveform, namely the area. Hatib et al. also note that a partial consequence of Cohen's greatly-simplified input signal to his recursive model is the need for a complicated transfer function model, which involves many zeroes, many poles, and, consequently, design and computational complexity.
However, Applicants note that the cardiac output estimation apparatus and methods described in U.S. Patent Application Publication No. 20050124903 to Roteliuk et al., U.S. Patent Application Publication No. 20050124904 to Roteliuk, U.S. Patent Application Publication No. 20060235323 to Hatib et al., U.S. Patent Application Publication No. 20080015451 to Hatib et al. (commonly owned by Edwards Life Sciences Corporation, hereinafter “Edwards”) and in Cohen et al. explicitly assume an impulsive input flow waveform. Furthermore, the methods of Edwards and Cohen require a fixed sampling rate, i.e., the rate at which the impulsive input flow waveform is generated and/or sampled. There is a need for CO and TPR estimation methods that do not require the assumption of such an input waveform, and that do not require fixed sampling rates. The methods of Cohen and Edwards also explicitly use actual arterial blood pressure waveforms, which make them more susceptible to noise and artifacts inherent in these waveforms. There is a need for CO and TPR estimation methods that use parameters or variables derived from blood pressure waveforms instead of blood pressure waveforms that are sampled at a very high rate, e.g., 90 Hz or greater within each cycle.
The Edwards patents, collectively, and U.S. Pat. No. 5,400,793 to Wesseling (hereinafter “Wesseling”) assume a 3-element Windkessel model in which a value for the input impedance of the model is either assumed or estimated. As the number of elements in a model increases, so does the complexity of the processing tasks that must be carried out to estimate CO or TPR. Therefore, the parameters and variables in this model cannot be easily estimated without making several assumptions, and requiring more input data than may be available in settings such as critical care units. The Edwards patents and Wesseling also describe calibration schemes for calibrating uncalibrated cardiac output, i.e., for calculating a multiplicative calibration factor that is used to obtain absolute cardiac output from proportional or relative cardiac output. In Edwards and Wesseling, the calibration scheme is dependent on coarse patient-specific data, e.g., height, body mass, age, gender. Wesseling's calibration factor has 3 parameters. In Edwards, the calibration factor furthermore requires the calculation of moments of the arterial blood pressure waveform. The calibration factors described in Edwards and Wesseling are complicated functions of three or more parameters which require several (at times, patient-specific) inputs. The Wesseling calibration factor is only grossly correlated to the cardiovascular system model he describes. There is still a need for simpler calibration factors that require fewer inputs and/or patient-specific parameters.
Although many CO estimation methods exist, as described above, there is still a need for CO estimation algorithms that are robust, and that effectively exploit both inter-cycle and intra-cycle variations in the blood pressure waveform. Thus, there is a need for CO and TPR estimation methods that use parameters or variables derived from blood pressure waveforms instead of highly-sampled blood pressure waveforms themselves. There also exists a need for CO estimation algorithms in which relative cardiac output estimates can be easily calibrated to obtain absolute cardiac output estimates. Thus, there is still a need for simpler calibration factors that require fewer inputs and/or patient-specific parameters. Current cardiac output estimation algorithms are not robust in the sense that they may perform well on a particular data set, but poorly on a different data set. There have been many methods in the past that seemed promising, but turned out not to work robustly. Furthermore, these CO estimation algorithms generally exploit either inter-cycle or intra-cycle variability. Currently, there are no algorithms for estimating cardiac output or total peripheral resistance that effectively exploit both inter-cycle and intra-cycle variations in the ABP waveform to estimate CO or TPR.